Physiologic oxygen measurement is important for many reasons, as follows:
The transfer function (FIG. 1) is the fundamental determinant of oxygen transport and distribution.
Adsorption of O.sub.2 by heme is the most widely used mechanism of oxygen storage and transport throughout the animal kingdom.
The corresponding protein change (globin) embedding the heme controls its adsorptive characteristics, and determines the shape of the transfer function, thus suiting the heme to the needs of a particular species.
The globin chain also is part of a control loop to adjust the curve to biochemical signals, most significantly pH, 2,3-di-phosphoglycerate and CO.sub.2.
In people, approximately 200 genetic variants of hemoglobin are known; most are innocuous, some are pathologically severe because of alteration of the transfer function (sickle cell disease, etc.).
Direct measurement of P.sub.O.sbsb.2 is therefore necessary to observe the oxygen transport behavior in an individual in any physiologic investigation.
Moreover, adequate tissue oxygenation is one of the most important short-range concerns in a variety of surgical and intensive care situations, requiring either quick response sampling or continuous monitoring of P.sub.O.sbsb.2 levels.
A number of techniques and systems are known, but none of these is entirely suitable. For example:
The Clark electrode (membrane-diffusion, amperometric) does not lend itself to small size.
The diffusion dependence is subject to calibration and drift problems.
A strictly potentiometric (redox) electrode has specificity difficulties.
Haase, U.S. Pat. No. 4,201,222 discloses an optical catheter, including a fiber optic bundle, adapted to be inserted into a blood vessel of a living body for measuring the partial pressure of oxygen gas in the blood stream. The catheter comprises a semipermeable wall member for excluding the entry therethrough of blood liquid while permitting passage of blood gases. The intensity of a reflected visible light beam entering the optical fiber bundle, when compared to the intensity of the incident beam, is said to accurately correspond to the partial pressure of the oxygen gas in the bloodstream.
Mori, U.S. Pat. No. 3,814,081 discloses an optical catheter for measuring the percentage content of oxygen saturating the blood stream of a living animal body. An illuminating fiber optic system and a light receiving system are arranged closely adjacent to one another. The tip of the catheter is inserted into a blood-carrying organ of the animal body. The degree of oxygen saturation is measured by a light absorption spectroscopic detemination of light waves which are reflected from the blood stream and received by an optical fiber bundle.
Ostrowski et al. U.S. Pat. No. 3,807,390 disclose a fiber optic catheter for monitoring blood oxygen saturation in a human blood stream, in vivo, by insertion of the catheter tip into the cardiovascular system of the living body.
Willis et al. U.S. Pat. No. 4,033,330 is of general interest in showing a transcutaneous optical pH measuring device for determining blood pH or carbon dioxide concentration in the blood. Fostick U.S. Pat. No. 4,041,932 is likewise of general interest in teaching an apparatus used to measure and monitor the concentration and partial pressure of gases, such as oxygen and carbon dioxide in arterial blood vessels, and the pH of the blood during various time periods.
The P.sub.O.sbsb.2 electrode literature is enormous, but there is still not a suitable electrode available.
Oxygen measurement by luminescence quenching has also been suggested. The idea originated in the 1930's, but has had relatively little use, although oxygen quenching of fluorescence is widely recognized as a nuisance. Stevens U.S. Pat. No. 3,612,866 discloses an apparatus for measuring the oxygen content concentration of liquids or gases based on the molecular luminescence quenching effect of gaseous oxygen on aromatic molecules, derivatives of such aromatics and aliphatic ketones.
Other applications of luminescence quenching for oxygen determination include:
1. Original observation of effect--dyes adsorbed on silica gel: H. Kautsky and A. Hirsch in early 1930's, e.g. H. Kautsky and A. Hirsch, Z. fur anorg. u. allgem. Chemie 222, 126-34, 1935.
2. Measurement of O.sub.2 produced by illumination of algae: M. Pollack, P. Pringsheim and D. Terwood, J. Chem. Phys., 12, 295-9, 1944.
3. Catalog of oxygen quenching sensitivities of organic molecules of scintillation interest: I. B. Berlman, "Handbook of Fluorescence Spectra of Aromatic Molecules", Academic Press, 1965.
4. O.sub.2 measured down to 10 .sup.-5 torr with acriflavin on acrylic sheet: Gy. Orban, Zs. Szentirmay and J. Patko, Proc. of the Intl. Conf. on Luminescence, 1966, v. 1, 611-3, 1968.
5. Diffusion coefficient of O.sub.2 in acrylics measured by observing the phosphorescence of rods: G. Shaw, Trans. Faraday Soc. 63, 2181-9, 1967.
6. O.sub.2 permeability of acrylic films measured by quench rate vs. P.sub.O.sbsb.2 : P. F. Jones, Polymer Letters 6, 487-91, 1968.
7. P.sub.O.sbsb.2 measuring instrument based on fluoranthene adsorbed on plastic films and porous vycor: I. Bergman, Nature 218,396, 1968.
8. Pyrenebutyric acid used as probe for measuring intracellular O.sub.2 : J. A. Knopp and I. A. Longmuir, Biochimica et Biophysica Acta, 279, 393-7, 1972.
9. Physiological P.sub.O.sbsb.2 measurement using DMF solutions of pyrenebutyric acid in various membrane-enclosed forms, D. W. Lubbers and N. Opitz, Z. Naturf. 30c, 532-3, 1975.